Background The brain undergoes dynamic and requisite changes into the early twenties that are associated with improved cognitive efficiency, particularly in prefrontal regions that are still undergoing neuromaturation. As alcohol consumption is typically initiated and progresses to binge drinking during this time, the objective of the present study was to investigate the impact of binge alcohol consumption on frontal lobe cortical thickness in emerging adults. Methods Twenty-three binge drinking (BD; 11 females, mean age 21.5 ± 1.4) and thirty-one light drinking (LD; 15 females, mean age 21.9 ± 1.6) emerging adults underwent high-resolution magnetic resonance imaging at 3 Tesla. Cortical surface reconstruction and thickness estimation were performed using Freesurfer for three a priori brain regions of interest: bilateral anterior cingulate cortex (ACC), posterior cingulate cortex (PCC) and parieto-occipital sulcus (POS). Cortical thickness measurements were then compared between BD and LD groups. Results Cortical thickness was significantly lower in BD than LD in the right middle ACC (mid-ACC; p≤0.05) and in the left dorsal PCC (dPCC; p≤0.01). No significant differences in cortical thickness were observed in the POS. Cortical thickness in the mid-ACC correlated negatively with higher quantity and frequency of drinks consumed (p<0.01), and positively with the number of days elapsed since most recent use (p<0.05). Furthermore, less cortical thickness in the mid-ACC in the BD group alone correlated with reported patterns of high quantity and frequency of alcohol consumption (p≤0.05). Conclusions Findings suggest that past and recent patterns of intermittent heavy alcohol consumption are associated with less frontal cortical thickness (i.e. ‘thinness’) of the right mid-ACC and left dPCC in emerging adults, but not the POS. While cortical thinness could have predated binge drinking, this pattern of maladaptive consumption may have acute neurotoxic effects that interfere with the finalization of neuromaturational processes in the vulnerable frontal cortex, resulting in increased microarchitectural pruning.

Previous findings in rats suggest that the rostral basolateral amygdala (rBLA) and prelimbic prefrontal cortex (plPFC) are likely components of cue reinstatement circuitry based on bilateral inactivation of each site alone. In the present investigation, we examined whether the rBLA and plPFC interact to regulate reinstatement of cocaine-seeking behavior elicited by re-exposure to a combination of discrete and contextual cocaine-paired cues. After establishing stable baseline responding under a second-order schedule of cocaine reinforcement and cue presentation, rats underwent response-extinction training in which cocaine and cocaine-paired cues were withheld. To test the interaction, rats with asymmetric cannulae placements in the rBLA and plPFC received vehicle or lidocaine infusions prior to reinstatement testing during which cocaine-paired cues were presented, in the absence of cocaine availability, under a second-order schedule. Asymmetric inactivation of the rBLA and plPFC significantly attenuated reinstatement of cocaine-seeking behavior relative to vehicle treatment. As expected, inactivation of the rBLA or plPFC in rats with unilateral cannulae placements did not disrupt reinstatement relative to vehicle treatment. Findings propose critical intrahemispheric interaction between the rBLA and plPFC in regulating reinstatement of cocaine-seeking behavior elicited by re-exposure to drug-paired cues.

Associations between cocaine and cues facilitate development and maintenance of addiction. We hypothesized that the ventral hippocampus is important for acquisition of these associations. Rats were trained to self-administer cocaine, with or without pre-exposure to distinct sets of cocaine- and saline-paired contextual cues. Next, rats were conditioned for 3 days with the distinct sets of contextual cues paired with cocaine and saline along with distinct discrete cues. Vehicle or lidocaine was infused into the ventral hippocampus prior to conditioning sessions. Following extinction, reinstatement of cocaine-seeking behavior was examined following exposure to contextual cues, discrete cues, or their combination. Inactivation of the ventral hippocampus during conditioning blocked acquisition of the association between cocaine and cocaine-paired contextual cues in that only lidocaine-treated rats with short-term cue exposure failed to reinstate responding in the presence of cocaine-paired contextual cues. Lidocaine also prevented rats in both cue exposure groups from discriminating between cocaine- and saline-paired contextual cues during reinstatement tests. Reinstatement induced by cocaine-paired discrete cues or by contextual and discrete cues together was not impaired for either cue exposure condition. The hippocampus is important for acquisition of the association between cocaine and context and in maintaining discrimination between cocaine-relevant and -irrelevant contextual cues.